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PubMed2001

Morphological identification of nitric oxide sources and targets in the cat oculomotor system.

Nitric oxide (NO) production by specific neurons in the prepositus hypoglossi (PH) nucleus is necessary for the correct performance of eye movements in alert cats. In an attempt to characterize the morphological substrate of this NO function, the distribution of nitrergic neurons and NO-responding neurons has been investigated in different brainstem structures related to eye movements. Nitrergic neurons were stained by either immunohistochemistry for NO synthase I or histochemistry for reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase. The NO targets were identified by cyclic guanosine monophosphate (cGMP) immunohistochemistry in animals treated with a NO donor immediately before fixation of the brain. Connectivity between cells of the NO-cGMP pathway was analyzed by injections of the retrograde tracers horseradish peroxidase or fast blue in different structures. The motor nuclei commanding extraocular muscles did not contain elements of the NO-cGMP pathway, except for some scattered nitrergic neurons in the most caudal part of the abducens nucleus. The PH nucleus contained the largest number of nitrergic cell bodies and a rich neuropil, distributed in two groups in medial and lateral positions in the caudal part, and one central group in the rostral part of the nucleus. An abundant cGMP positive neuropil was the only NO-sensitive element in the PH nucleus, where no cGMP-producing neuronal cell bodies were observed. The opposite disposition was found in the marginal zone between the PH and the medial vestibular nuclei, with a large number of NO-sensitive cGMP-producing neurons and almost no nitrergic cells. Both nitrergic and NO-sensitive cell bodies were found in the medial and inferior vestibular nuclei and in the superior colliculus, whereas the lateral geniculate nucleus contained nitrergic neuropil and a large number of NO-sensitive cell bodies. Some of the cGMP-positive neurons in the marginal zone and medial vestibular nucleus projected to the PH nucleus, predominantly to the ipsilateral side. These morphological findings may help to explain the mechanism of action of NO in the oculomotor system.

Abducens Nerve↗
PubMed2006

Ontogeny of hypothalamic-hindbrain feeding control circuits.

Ingestive behavior is a complex product of distributed central control systems that respond to a diverse array of internal and external sensory stimuli. Relatively little is known regarding the pathways and mechanisms by which relevant signals are conveyed to the neural circuits that ultimately control ingestive motor output. This report summarizes findings regarding the postnatal development of descending hypothalamic inputs to the hindbrain dorsal vagal complex (DVC). Evidence accumulated primarily in rats indicates that descending neural projections from the hypothalamus to the DVC are both structurally and functionally immature at birth. The progressive postnatal maturation of these projections occurs in parallel with newly emerging physiological and behavioral responsiveness to treatments and stimuli that affect food intake in adults. Thus, the postnatal emergence of new feeding controls may reflect the emerging access of these controls to DVC neural circuits.

Animals↗
PubMed1992

Different modes of dampening influence from baroreceptors are determined by the functional organization of the NTS neuronal network.

Simultaneous recordings of several neurones of the first relay station of baroreceptor afferents show that its general activity-dampening influence is realized via the common brainstem system (CBS) which itself controls the processing on the neurones of the nucleus of the solitary tract (NTS). This feedback system maintains the degree of activity which is necessary for the ongoing behaviour as long as it fits to the environmental situation. The output of the NTS is determined partly by the CBS, partly by the properties of the peripheral afferent input, partly by the dynamic functional organization of the local circuits and partly by influences from other brain areas.

Action Potentials↗
PubMed2004

Optical survey of neural circuit formation in the embryonic chick vagal pathway.

The multiple-site optical recording technique with a voltage-sensitive dye, NK2761, was used to survey functional organization of neural circuits related to the vagus nerve in the embryonic chick brainstem. When we stimulated the vagus nerve, in addition to the responses in the vagal sensory nucleus (nucleus of the tractus solitarius (NTS)) and motor nucleus (dorsal motor nucleus of the vagus nerve (DMNV)) on the stimulated side, another response area was discriminated at the level of the pons/rostral medulla on the contralateral side. Characteristics of the contralateral optical signals suggested that they correspond to the neural activity in the second/higher-ordered nucleus of the vagal pathway, possibly the parabrachial nucleus, which receives inputs from the NTS. Blockade of non-N-methyl-d-aspartate (NMDA) receptors abolished the responses on the contralateral side, together with the postsynaptic firing in the NTS, suggesting the significance of non-NMDA receptor function in sensory information transfer via the NTS. The responses on the contralateral side were first detected from the 7-day-old embryonic stage, when the glutamatergic excitatory postsynaptic potentials were first expressed in the NTS. The results suggest that the synaptic pathway from the NTS to the contralateral nucleus is already generated when the primary vagal afferents make functional synapses on NTS neurons.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2006

Metachronal coupling between spinal neuronal networks during locomotor activity in newborn rat.

In the present study, we investigate spinal cord neuronal network interactions in the neonatal rat during locomotion. The behavioural and physiological relevance of metachronally propagated locomotor activity were inferred from kinematic, anatomical and in vitro electrophysiological data. Kinematic analysis of freely behaving animals indicated that there is a rhythmic sequential change in trunk curvature during the step cycle. The motoneurons innervating back and tail muscles were identified along the spinal cord using retrograde labelling. Systematic multiple recordings from ventral roots were made to determine the precise intrinsic pattern of coordination in the isolated spinal cord. During locomotor-like activity, rhythmic ventral root motor bursts propagate caudo-rostrally in the sacral and the thoracic spinal cord regions. Plotting the latency as a function of the cycle period revealed that the system adapts the intersegmental latency to the ongoing motor period in order to maintain a constant phase relationship along the spinal axis. The thoracic, lumbar and sacral regions were capable of generating right and left alternating motor bursts when isolated. Longitudinal sections of the spinal cord revealed that both the bilateral antiphase pattern observed for the sacral region with respect to the lumbar segment 2 as well as the intersegmental phase lag were due to cross-cord connections. Together, these results provide physiological evidence that the dynamic changes observed in trunk bending during locomotion are determined by the intrinsic organization of spinal cord networks and their longitudinal and transverse interactions. Similarities between this organization, and that of locomotor pattern generation in more primitive vertebrates, suggest that the circuits responsible for metachronal propagation of motor patterns during locomotion are highly conserved.

Algorithms↗
PubMed1994

A computer model of amplitude-modulation sensitivity of single units in the inferior colliculus.

A computer model is presented of a neural circuit that replicates amplitude-modulation (AM) sensitivity of cells in the central nucleus of the inferior colliculus (ICC). The ICC cell is modeled as a point neuron whose input consists of spike trains from a number of simulated ventral cochlear nucleus (VCN) chopper cells. Input to the VCN chopper cells is provided by simulated spike trains from a model of the auditory periphery [Hewitt et al., J. Acoust. Soc. Am. 91, 2096-2109 (1992)]. The performance of the model at the output of the auditory nerve, the cochlear nucleus and ICC simulations in response to amplitude-modulated stimuli is described. The results are presented in terms of both temporal and rate modulation transfer functions (MTFs) and compared with data from physiological studies in the literature. Qualitative matches were obtained to the following main empirical findings: (a) Auditory nerve temporal-MTFs are low pass, (b) VCN chopper temporal-MTFs are low pass at low signal levels and bandpass at moderate and high signal levels, (c) ICC unit temporal-MTFs are low pass at low signal levels and broadly tuned bandpass at moderate and high signal levels, and (d) ICC unit rate-MTFs are sharply tuned bandpass at low and moderate signal levels and flat at high levels. VCN and ICC units preferentially sensitive to different rates of modulation are presented. The model supports the hypothesis that cells in the ICC decode temporal information into a rate code [Langner and Schreiner, J. Neurophysiol. 60, 1799-1822 (1988)], and provides a candidate wiring diagram of how this may be achieved.

Animals↗
PubMed1998

Ventrolateral medullary respiratory network and a model of cough motor pattern generation.

The primary hypothesis of this study was that the cough motor pattern is produced, at least in part, by the medullary respiratory neuronal network in response to inputs from "cough" and pulmonary stretch receptor relay neurons in the nucleus tractus solitarii. Computer simulations of a distributed network model with proposed connections from the nucleus tractus solitarii to ventrolateral medullary respiratory neurons produced coughlike inspiratory and expiratory motor patterns. Predicted responses of various "types" of neurons (I-DRIVER, I-AUG, I-DEC, E-AUG, and E-DEC) derived from the simulations were tested in vivo. Parallel and sequential responses of functionally characterized respiratory-modulated neurons were monitored during fictive cough in decerebrate, paralyzed, ventilated cats. Coughlike patterns in phrenic and lumbar nerves were elicited by mechanical stimulation of the intrathoracic trachea. Altered discharge patterns were measured in most types of respiratory neurons during fictive cough. The results supported many of the specific predictions of our cough generation model and suggested several revisions. The two main conclusions were as follows: 1) The Bötzinger/rostral ventral respiratory group neurons implicated in the generation of the eupneic pattern of breathing also participate in the configuration of the cough motor pattern. 2) This altered activity of Bötzinger/rostral ventral respiratory group neurons is transmitted to phrenic, intercostal, and abdominal motoneurons via the same bulbospinal neurons that provide descending drive during eupnea.

Animals↗
PubMed1999

Optical mapping of neural network activity in chick spinal cord at an intermediate stage of embryonic development.

We have applied multiple-site optical recording of transmembrane potential changes to recording of neuronal pathway/network activity from embryonic chick spinal cord slice preparations. Spinal cord preparations were dissected from 8-day-old chick embryos at Hamburger-Hamilton stage 33, and transverse slice preparations were prepared with the 13th cervical spinal nerve or with the 2nd or 5th lumbosacral spinal nerve intact. The slice preparations were stained with a voltage-sensitive merocyanine-rhodanine dye (NK2761). Transmembrane voltage-related optical (dye-absorbance) changes evoked by spinal nerve stimulation with positive square-current pulses using a suction electrode were recorded simultaneously from many loci in the preparation, using a 128- or 1,020-element photodiode array. Optical responses were detected from dorsal and ventral regions corresponding to the posterior (dorsal) and anterior (ventral) gray horns. The optical signals were composed of two components, fast spike-like and slow signals. In the dorsal region, the fast spike-like signal was identified as the presynaptic action potential in the sensory nerve and the slow signal as the postsynaptic potential. In the ventral region, the fast spike-like signal reflects the antidromic action potential in motoneurons, and the slow signal is related to the postsynaptic potential evoked in the motoneuron. In preparations in which the ventral root was cut microsurgically, the antidromic action potential-related optical signals were eliminated. The areas of the maximal amplitude of the evoked signals in the dorsal and ventral regions were located near the dorsal root entry zone and the ventral root outlet zone, respectively. Quasiconcentric contour-line maps were obtained in the dorsal and ventral regions, suggesting the functional arrangement of the dorsal and ventral synaptic connections. Synaptic fatigue induced by repetitive stimuli in the ventral synapses was more rapid than in the dorsal synapses. The distribution patterns of the signals were essentially similar among C13, LS2, and LS5 preparations, suggesting that there is no difference in the spatiotemporal pattern of the neural responses along the rostrocaudal axis of the spinal cord at this developmental stage. In the ventral root-cut preparations, comparing the delay times between the ventral slow optical signals, we have been able to demonstrate that neural network-related synaptic connections are generated functionally in the embryonic spinal cord at Hamburger-Hamilton stage 33.

Animals↗
PubMed2006

Trigeminal neuropathic pain alters responses in CNS circuits to mechanical (brush) and thermal (cold and heat) stimuli.

Functional magnetic resonance imaging was used to study patients with chronic neuropathic pain involving the maxillary region (V2) of the trigeminal nerve in patients with spontaneous pain and evoked pain to brush (allodynia). Patients underwent two functional scans (2-3 months apart) with mechanical and thermal stimuli applied to the affected region of V2 and to the mirror site in the unaffected contralateral V2 region, as well as bilaterally to the mandibular (V3) division. Patients were stimulated with brush, noxious cold, and noxious heat. Significant changes were observed in regions within and outside the primary trigeminal sensory pathway. Stimulation to the affected (neuropathic) side resulted in predominantly frontal region and basal ganglia activation compared with the control side. The differences were consistent with the allodynia to brush and cold. A region of interest-based analysis of the trigeminal sensory pathway revealed patterns of activation that differentiated between the affected and unaffected sides and that were particular to each stimulus. Activation in the spinal trigeminal nucleus was constant in location for all pain stimuli. Activation in other brainstem nuclei also showed differences in the blood oxygenation level-dependent signal for the affected versus the unaffected side. Thus, sensory processing in patients with trigeminal neuropathic pain is associated with distinct activation patterns consistent with sensitization within and outside of the primary sensory pathway.

Adult↗
PubMed1994

Evidence of interaction between human lumbosacral and cervical neural networks during gait.

Changes in H-max amplitude resulting from alteration in arm position have been used with changes in gait double support durations resulting from similar changes in arm posture to investigate interaction, if any, between the lumbosacral and cervical neural networks in seven normal subjects. Since the reflex and gait responses of each lower limb were altered by changes in upper limb position, it was suggested that in humans also, there may be interaction not only in a static situation, but also during gait between the lumbosacral and cervical neural networks. The responses of the right leg were always greater than those of the left leg irrespective of the arm position; This retention of inter-limb relation may indicate a dominance of the lumbosacral neural network over its cervical counterpart.

Adult↗
PubMed1993

Observations on the survival of grafted embryonic motoneurons in the spinal cord of developing rats.

The sciatic nerve of newborn rats was injured unilaterally. Small solid grafts of ED-12 embryonic spinal cord prelabeled with 5-bromo-2'-deoxyuridine (BrDUr) were inserted into the host's hemicord on the side of the sciatic nerve injury on PD5-12. Each graft was connected to a neuromuscular implant, which in group 1 consisted of the soleus muscle and its nerve taken from the healthy leg of the same rat pup, whereas in group 2 the soleus neuromuscular implant was taken from an immunocompatible adult rat. Six to 12 weeks later the neurons extending axons into the nerve-muscle implants were retrogradely labeled with fast blue and diamidino yellow. The embryonic origin of these neurons was ascertained by visualizing BrDUr using an immunocytochemical method. The grafts survived well and contained many BrDUr-positive neurons. No retrogradely labeled neurons were found in group 1 animals. In group 2 (animals with adult implants) numerous retrogradely labeled neurons were present in the host's neuropil. Despite the access to the target there were no BrDUr-positive cells of embryonic origin that contained the retrograde labels. Indeed no motoneuron-like cells of embryonic origin were seen in the host neuropil in any of the animals which received a graft at the age of 5-12 days. This contrasts with previous studies where the grafts were introduced into the adult spinal cord and motoneuron-like cells of embryonic origin were present in the host neuropil. Thus, it appears that the environment of the developing spinal cord is unfavorable for survival of embryonic motoneurons.

Amidines↗